February 6, 2001
How are children and adolescents different from adults? This was the question that framed the review of immune reconstitution given by NYU's Bill Borkowsky. The pattern of immune reconstitution in adults is fairly well understood. CD4 counts climb 100 to 250 cells in the first year, marked initially by an increase in memory cells and a decrease in activation. After 4 to 6 months, naive cells start to increase but only slowly return toward normal levels. In some studies, there is broadening of the T-cell receptor reservoir, but it is not consistent. In chronically-infected children and adolescents treated with HAART, there are some striking differences. CD4 cell increased in the first year average 320 to 650 cells in different studies. The increase is driven by a dramatic increase in naive cells, often to normal levels. Cells containing TREC increase strikingly, probably reflecting greater thymic activity. Borkowsky reviewed evidence that the increase in thymic size correlates with the increase in naive cells. TCR repertoire broadens fairly consistently in the limited number of studies. Skin test delayed hypersensitivity is less consistent, as in adults.
Borkowsky explored the clinical implications of this greater capacity for immune reconstitution with younger age. A number of studies show dramatic immune reconstitution even when therapy is begun after significant immune damage. CD4 cell rises are often maintained after virologic failure occurs if therapy is maintained, paralleling the "CD4 disconnect" phenomenon in adults explored by Steve Deeks and others. To Borkowsky, this suggests that we may be able to wait longer to institute therapy in children to decrease the rate at which we burn through drugs.
Given the challenging family situations and the difficulty with adherence, this is tempting. What needs to be factored into this decision are the issues surrounding growth, neurologic development, and the wide range of "B"-type symptoms that do not always clear with therapy. Nonetheless, this talk struck some of the same cords explored in other papers about adults trying to balance when to start therapy.
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